Every year in the United States, more than 10,000 people experience spinal cord injury (SCI), with an estimated 250,000 of those cases sufficiently severe to require wheelchair use. A majority of SCI patients are injured while under the age of 30 years and will often experience a normal lifespan, leading to extremely high medical costs over the course of a lifetime.
SCI is an extremely difficult condition to understand and manage in a clinical setting due to the multitude of injury mechanisms involved. In addition to the primary injury, it is thought that a complex array of secondary injury mechanisms account for the progression of damage from the central gray matter to the surrounding white matter that begins within minutes and persists long after primary injury. After several days to weeks, the initial injury can expand in size, leading to a scar-encapsulated cavity many times the size of the original lesion. The cavity is bounded by abnormally proliferating glial cells and primarily astrocytes, which can form a physical barrier to any potential neuronal regeneration. Suspected secondary injury mechanisms include hemorrhage, ischemia-reperfusion, excito-toxicity, demyelination, calcium mediated injury, disturbances in mitochondrial function, apoptosis and/or necrosis of neurons and oligodendrocytes, and inflammation.
Currently, only one therapeutic agent, methylprednisolone (MP), is widely considered standard therapy after traumatic SCI. MP is a synthetic glucocorticosteroid that has been subjected to several large-scale human clinical trials and showed minor clinical benefits when administered within 48 hours of SCI. However, questions regarding MP's efficacy persist due to controversy surrounding study design and analysis/interpretation of data from clinical trials. Therefore, continued investigation and evaluation of potential therapeutic agents for traumatic SCI is paramount. Accordingly, there is a need for methods to treat SCI.